The entire scientific community (save for a few) believes that even though there appears to be nuclear androgen binding proteins throughout the germ cell population of the spermatogenic cycle and epididymal spermatozoa, that they play no role in the development and maturation of mammalian spermatozoa. It is felt that the undeniable dependence of sperm cells upon androgens is served indirectly through androgen receptors in Sertoli cells (testis) and epithelial cells (epididymis). This viewpoint has strong (but not overwhelming) experimental support. This grant proposal takes the position that the substantial concentration of androgen receptors in sperm cells are unique; they become completely resistant to normal salt extraction during developments, apparently at spermatid stage 10 (rat), when the nucleus condenses sharply. By the time the spermatozoa reach the cauda epididymidis, the androgen receptor can be retrieved only by indefatigable fractionation and isolation of the nuclear protein matrix. Similar nuclear salt-resistant fractions of steroid binding activity in other tissues mediate the most significant physiological events. We intend therefore by nuclear exchange (validated by radioimmunoassay) to determine exactly where the nuclear binding resides in late spermatids and epididymal spermatozoa, when it becomes salt-resistant, whether it is as resistant to physiological adversity (castration, hypophysectomy, cryptepididimal reflection) as it is to chemical fractionation, and whether its concentration is subject to regulation by a sudden increase in testosterone, at stages prior to or after it has become salt-resistant. We do not yet intend to delineate exactly the physiological role served by this remarkable encasement of the androgen receptor, only to demonstrate that it is deliberate and ensures stabilization and protection of the receptor as the spermatozoa move out into an environment which daily becomes more androgen deficient. This study of the sperm androgen receptor deals in general with what may be the most important single function of the nuclear salt-resistant steroid receptor, and in particular with basic and neglected mechanisms of sperm development and maturation.